Soutenance de thèse:
Inferring forces from geometry in biology
Rudolf Podgornik, University of Ljubljana (Slovenia) and Chinese Academy of Sciences (Beijing, China)
Anđela Šarić, University College London (United Kingdom)
Clément Campillo, Université d’Évry Val d’Essonne (France)
Antonio De Simone, Scuola Internazionale Superiore di Studi Avanzati (Trieste, Italy)
Aurélien Roux, Université de Genève (Suisse)
Pierre Sens, Institut Curie (Paris, France)
Martin Lenz, CNRS and Université Paris-Sud (France)
Inter-molecular forces on which we have poor prior knowledge are often essential for the stability and evolution of biological assemblies. In this thesis, we focus on two such forces that are critically involved in the deformation of either biopolymers or membranes. We infer these forces by reconciling the geometry of such deformation with simple mechanical models.
In the first part of the thesis, we consider the attractive force between DNA molecules mediated by multivalent cations. This attraction is required to compensate DNA bending rigidity when packaging large quantities of DNA in comparatively small environments, such as the nuclei of sperm cells. In vitro, multivalent cations drive DNA condensation into dense toroidal bundles. Geometrical data on DNA toroidal bundles give access to the competition between inter-helical attraction and DNA bending rigidity. From these data, we infer inter-helical forces and argue that the toroid curvature weakens the adhesion between DNA molecules.
In the second part of the thesis, we turn to the binding force of a membrane remodeling protein complex, ESCRT-III, to cellular membranes. ESCRT-III proteins assemble into membrane-remodeling polymers during many cellular processes, ranging from HIV budding to cytokinesis. The mechanism by which ESCRT-III polymers deform membranes is still unclear. In vitro, ESCRT-III polymers can reshape spherical membrane vesicles into helical tubes. We argue that helical tubes result from the peculiar positioning of membrane-binding sites on the surface of ESCRT-III polymers. Furthermore, we infer the binding force between ESCRT-III and membrane from the geometry of helical tubes.